The central nervous system (CNS) of an animal, for example, human, contains several important receptor systems such as the glutamate, acetylcholine, GABAA, and NMDA receptor systems, and injury to the CNS as well as other diseases and disorders of the CNS could be quite serious including threat to life. For example, following a traumatic injury to the CNS, a cascade of physiological events can lead to neuronal loss, including, for example, an inflammatory immune response and excitotoxicity resulting from the initial impact of one or more of the above receptor systems. In addition, traumatic CNS injury can be accompanied by brain edema that enhances the cascade of injury and can lead to further secondary cell death and increased mortality of the animal.
An example of the CNS injury is traumatic brain injury (TBI) to the brain, which is a head injury caused by trauma to the brain. Symptoms of TBI include headache, confusion, dizziness, blurred vision, changes in mood, impairment of cognitive function such as memory, learning, and attention, nausea, convulsions or seizures, slurring of speech, numbness of extremities, and loss of coordination. While some symptoms appear immediately, others do not appear until days, months or even years after the TBI event. TBI is a major cause of preventable death and morbidity, and disability following injury in war zones, in sports and recreation, and general population falls and accidents. Secondary injury occurring hours and days after the head trauma occurs as a result of ischemia, blood brain barrier leakage and inflammatory/oxidative stress.
Attempts to treat diseases and disorders of the CNS, particularly TBI, that target neuroprotection following TBI have proven to be of little efficacy. The blood brain barrier (BBB) has been a cause of many drugs' ineffective translation from “promising” to “failure” in the treatment or prevention of various brain injury and other CNS disease or disorders. Much resources have been spent on developing drugs which when administered systemically have proven to be ineffective. This failure is believed to be due to the blockage of the drug by the BBB from reaching the CNS, wherein the blockage leads to inadequate concentration of the drug in the CNS.
The foregoing shows that there is an unmet need for a treatment modality that can effectively administer a drug to the CNS, thereby treating and/or preventing a disease or disorder of the CNS.